Neonatal Platelet Transfusion Indications Parisa Mohagheghi, Associate Professor, Iran University of Medical Sciences

There are many concerns about the normal or abnormal platelet counts in neonates and specially in preterm neonates and absolute criteria for platelet transfusion (PTXs) are not evidence based and is based almost entirely on ‘level 4 evidence’ (i.e., expert opinion and Reasoning) . So the policies for PTXs differ in different countries. The bleeding tendency in infants are not only related to platelet counts but also to their underlying disease, and for example in IUGR infants with thrombocytopenia there is a low risk of bleeding whereas it is a 10-20% incidence of intracranial hemorrhage in neonatal allouimmune thrombocytopenia (NAIT)

Normal Platelet Count It is generally accepted that human neonates have blood platelet counts within the same normal range as older children and adults (i.e., 150,000–450,000/μl). However, recent data suggest a lower normal limit of 120,000/μl for preterm neonates during the first days following birth. Using the conventional lower limit of 150,000/μl for normal values, below 1% of term neonates experience thrombocytopenia ; whereas 20–35% of preterm neonates admitted to a neonatal intensive-care unit (NICU) will have blood platelet counts less than 150,000/μl .

Classification Thrombocytopenia is classified as mild (100- 149000/μl) , moderate (50-99000/μl) , and severe (<50000/μl ). Among all thrombocytopenic preterm neonates, 25– 38% will have blood platelet counts less than 50,000/μl (i.e., severe thrombocytopenia) and will probably receive PTXs . A majority of platelet transfusions in neonates are prophylactic in those with no signs of clinical bleeding and with platelet counts greater than 50,000/μl.

Incidence Thrombocytopenia is the most common hematologic abnormality among sick, and in NICU it is as high as 35% and it reaches 70% in newborns with birth weight <1000g.

Intracranial hemorrhage (ICH) Quantitative and qualitative disorders of platelet may cause significant bleeding in different organs and the most serious is intracranial bleeding. Risk of ICH increases (from 48% in 78% ) in preterm infants with platelet count< 100,000/mL. In allouimmune Thrombocytopenia approximately 10- 20% of affected fetuses have ICH, 25-50% occur in utero. Veerareddy S, Pandya P. Thrombocytopenia in pregnancy: fetal and neonatal allouimmune thrombocytopenia. In: Disorders of thrombosis and hemostasis in pregnancy, springer 2012

Indications for PTx In one randomized, controlled trial in preterm neonates, Andrew et al. randomized preterm infants to either a treatment group where they transfused platelets to keep the platelet count greater than 150,000/μL or a control group where they transfused platelets to maintain the platelet count above 50,000/μL. This investigation revealed no difference in incidence or severity of IVH in the two groups.

Platelet count (×103//μl) neonates Immune Status Bleeding Platelet count (×103//μl)   NAIT ATIP No Yes Transfuse if bleeding Transfuse if bleeding /IVIG not available Consider PTX Transfuse <30 If bleeding If unstable, bleeding If W<1000 g postnatal age <1 Unstable (IVH grade 3 or 4) Associated coagulopathy Surgery required 30–49

Platelet Bleeding Immune Status Yes No ATIP NAIT 50–99 Transfuse If bleeding Do not Transfuse

Preparation: Platelets are obtained by two different mechanisms. One process entails centrifugation of whole blood and yields at least 5.5 × 1010 platelets in 40-70 mL of plasma. One unit of WBD platelets is sufficient for a neonate. The second process for obtaining platelets is via apheresis, in which an apheresis machine extracts platelets from a donor’s blood and then returns remaining blood back to the donor. A unit of apheresis- derived platelets contain greater than 3.0 × 1011 platelets in about 200 mL of plasma.

The content of one unit of apheresis platelet unit is equivalent to approximately 6 units of WBD platelets. A dose of 5–10 mL/kg of WBD platelets will raise the plasma platelet count from 50,000/μL to 150,000/μL.

Storage Platelets are stored at room temperature (20–24 °C). Because they are not refrigerated, platelets are the blood product most prone to bacterial contamination and have a limited shelf life of 5 days. For the same reason, once a unit of platelets is accessed, it must be transfused within 4 h. They also need to be gently agitated during storage to prevent aggregation

Compatibility ABO compatibility for platelet concentrate is not necessary, but ABO compatible platelet provides higher platelet increments. Small amounts of RBCs (0.2-0.3 mL) are present in WBD platelets and can cause Rh sensitization in a Rh negative recipient. Administration of Rh immunoglobin (RhIg intramuscular dose:120 IU/mL RBC) should be strongly considered for Rh negative neonates, especially females, within 72 hours of exposure to Rh- positive RBCs through a WBD platelet transfusion.

When apheresis platelets are used, immunoprophylaxis for Rh sensitization should be discouraged because they contain much less RBC volume than the minimum volume required to cause Rh alloimmunization.

Platelet in NAIT Antigen-negative platelets are considered optimal for the prevention of hemorrhage in newborns with suspected NAIT. To meet this need, transfusion services have attempted to stock HPA-1a–negative and HPA-5b–negative donor platelet concentrates for emergency use. However, this remains a logistic challenge, given the relatively low frequency (approximately 2.5%) of HPA-1a–negative donors. As an alternative to HPA-1a–negative donor platelets, transfusion of maternal platelets is recommended. However, these platelets must also be prepared within a short time, and the appropriate facilities are available 24 hours a day only in specialized centers. In addition, if maternal platelets are used, it is absolutely essential that they be washed to remove antibody-containing maternal plasma, tested for transfusion relevant infection markers, and irradiated. Therefore, in cases of unexpected NAIT, maternal platelet concentrates are only available after a delay of 12 to 48 hours.

Platelet in NAIT It is recommended to use random platelet concentrates in newborns suspected to have NAIT with platelet counts below 30×106/ μL while waiting for matched (HPA-1a–negative, HPA-5b–negative) platelets if these are not immediately available. Combining this transfusion with IVIG may achieve a transient rise

Ideal platelet The specifications for an ideal platelet concentrate are as follows (quality control): Volume :40-70 ml; Platelet yield:>5.5 × 1010 ; Leucocytes:< 108; RBC:< 0.5 ml; pH: > 6.0 Leukocyte-reduced, irradiated

Factors affecting response Some factors affect response to platelet transfusion and the following conditions may not give desired results of platelet transfusion: Bleeding Fever Infection Splenomegaly Disseminated intravascular coagulation (DIC) Uremia Antibodies to human platelet antigens (HPA) or human leucocyte antigens (HLA)

Harmful effects Increased incidence of bacterial infection Exacerbation of inflammatory injury Mortality rate in thrombocytopenic NICU patients who received PTXs increased dramatically with the number of PTXs Baer VL, Lambert DK, Henry E, et al. Do platelet transfusions in the NICU adversely affect survival? J Perinatol 2007

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